Synthesis, in silico and in vitro assessment of new quinazolinone tethered triazole derivatives as anticancer agents

A new series of quinazolinone–triazole hybrids (5a–q) was synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition. O-Propargylation of compound 1 afforded intermediate 2, which underwent CuAAC with azidobenzenes (3a–q), followed by condensation with anthranilamide to yield the target molecules in good yields. Structures were confirmed by standard spectroscopic techniques. Anticancer evaluation against MCF-7 cells (MTT assay) identified 5a, 5n, and 5o as the most active derivatives, with IC50 values of 17.21, 20.23, and 14.92 μM, respectively. Docking studies showed strong binding affinities toward CDK2, supported by key hydrogen-bonding and hydrophobic interactions. A 100 ns molecular dynamics simulation further validated the stable binding of the 5o–CDK2 complex. Overall, the study introduces a novel class of quinazolinone–triazole derivatives with promising CDK2-targeted anticancer potential, highlighting 5o as a lead candidate for further optimization.